The current research plan proposes study of acid finger protein (AFP), a candidate for the human disorder hemochromatosis. The gene was identified by positional cloning methods within the hemochromatosis locus near the Class I region of the major histocompatibility complex on 6p2l.3. Analysis of the cDNA and encoded protein sequence has demonstrated remarkable similarity to previously described metal dependent DNA binding proteins. Preliminary data suggests that AFP may be involved with iron metabolism. Within the 3' untranslated region of the cDNA exists a sequence motif resembling an iron responsive element Moreover, northern data suggests that expression of AFP in cultured cells is dependent on iron concentration within the culture media. Specific plans for study include implementation of methods to detect AFP mutations in hemochromatosis patients, creation of animal models of AFP deficiency, characterization of AFP iron responsiveness, and determination of DNA and protein binding targets.